Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Soonchunhyang University Bucheon Hospital, |
RCV000490390 | SCV000267562 | uncertain significance | Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4 | 2016-03-18 | criteria provided, single submitter | reference population | |
Illumina Laboratory Services, |
RCV000128463 | SCV000427556 | likely benign | Tooth agenesis, selective, 4 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Illumina Laboratory Services, |
RCV000270809 | SCV000427557 | benign | SchC6pf-Schulz-Passarge syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Illumina Laboratory Services, |
RCV000325824 | SCV000427558 | benign | Odonto-onycho-dermal dysplasia | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Labcorp Genetics |
RCV000490390 | SCV001013761 | benign | Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4 | 2025-01-09 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001555273 | SCV001776659 | likely pathogenic | not provided | 2024-07-11 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34878701, 33932139, 31103801, 28944914, 31180159, 24312213, 30555066, 24449199, 29367877, 23401279, 24311251, 27657131, 29178643, 25629078, 34426522, 33034246, 24458874, 35537890, LiuH[article]2022, 36071541, 34834569, 34184264, 35546689, 33329022, 24043634, 36143186, 37228816, 37005710, 38163170, 36832485, 38280992) |
Stomatology Center, |
RCV003233110 | SCV003930329 | pathogenic | Tooth agenesis, selective, 2 | criteria provided, single submitter | research | We used whole exome sequencing to compare tooth loss gene loci between two brothers with hypophidrotic ectodermal dysplasia (HED), analyze the difference of tooth loss phenotype, and explore its mechanism. wes showed that an EDA mutation was found in both older and younger brothers (c.878T>G), and the compound heterozygous mutation of WNT10A (c.511C>T and c.637G>A) Found only in the elder brothers. Prediction of secondary and tertiary structures of the WNT10A variants (p. R171C, p.G213S) indicated the impaired function of the molecule. The elder brothers have a more severe tooth loss phenotype than younger brothers. It has been reported that eda c.878T>G mutation caused HED (PMID: 30526585). We believe that EDA is the main pathogenic gene in the two patients, and the compound heterozygous WNT10A missense mutation can aggravate the HED phenotype caused by EDA mutation, resulting in a severe edentulous mandible phenotype in the elder brother. | |
OMIM | RCV000128463 | SCV000172165 | pathogenic | Tooth agenesis, selective, 4 | 2014-02-01 | no assertion criteria provided | literature only | |
Yale Center for Mendelian Genomics, |
RCV000845115 | SCV000987051 | uncertain significance | Tooth agenesis | 2014-09-15 | no assertion criteria provided | literature only | |
Department of Second Dental Center, |
RCV000128463 | SCV004023333 | uncertain significance | Tooth agenesis, selective, 4 | no assertion criteria provided | clinical testing | ||
Department of Second Dental Center, |
RCV000325824 | SCV004032521 | uncertain significance | Odonto-onycho-dermal dysplasia | no assertion criteria provided | clinical testing | ||
Prevention |
RCV004734670 | SCV005358819 | likely pathogenic | WNT10A-related disorder | 2024-03-19 | no assertion criteria provided | clinical testing | The WNT10A c.637G>A variant is predicted to result in the amino acid substitution p.Gly213Ser. This variant has been reported in the compound heterozygous state, with another variant in WNT10A (phase unknown), with variants in the EDA gene (phase unknown), and in the heterozygous state in individuals with mild ectodermal dysplasia or tooth agenesis (Patient 14, Plaisancié et al. 2013. PubMed ID: 23401279; Proband 52 and 53, He et al. 2013. PubMed ID: 2431221; Song et al. 2013. PubMed ID: 24043634; Family 1, Kantaputra et al. 2014. PubMed ID: 24311251; Yang et al. 2014. PubMed ID: 25629078; Yuan et al. 2017. PubMed ID: 29178643; Park et al. 2019. PubMed ID: 31103801). Of note, this variant has been reported in patients and in normal control populations (Song et al. 2013. PubMed ID: 24043634). Protein structure analysis predicted that this variant would alter protein structure (He et al. 2013. PubMed ID: 24312213). This variant is reported in 2.8% of alleles in individuals of East Asian descent in gnomAD including 14 homozygous individuals. This variant has conflicting interpretations in ClinVar ranging from likely pathogenic to uncertain significance to likely benign to benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/139576/). Taken together, we classify this variant as likely pathogenic. |